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Biomedical subjects

P E Hay

Publications and source records attributed to P E Hay.

At least 19 recordsLinked to original sources

Mycoplasma genitalium in chronic non-gonococcal urethritis.

Seventy-eight men with a history of chronic urethritis were referred for investigation. Of 52 men diagnosed as having persistent or recurrent non-gonococcal urethritis (NGU) at the time of referral, 11 (21%) were infected with Mycoplasma genitalium and three with Chlamydia trachomatis. Men who were M. genitalium-positive had not previously received less antibiotic, in terms of treatment duration, than those who were M. genitalium-negative, suggesting a possible resistance to the antibiotics given. In the current investigation, of 11 M. genitalium-positive men with persistent or recurrent NGU who were treated for four to six weeks with erythromycin, 500 mg four times daily, nine (82%) responded clinically and microbiologically, but later six relapsed without M. genitalium being detected. The results of observing and investigating a patient for about one year, the only one to have concurrent chlamydial and mycoplasmal infections, is presented, a feature being the intermittent persistence of the mycoplasma.

Adolescent↗

Mucosal and systemic immune responses to plasmid protein pgp3 in patients with genital and ocular Chlamydia trachomatis infection.

The circulating and cervical B cell responses to Chlamydia trachomatis plasmid protein pgp3 were characterized in children and adults with ocular or genital chlamydial infection using the enzyme-linked immunospot assay (ELISPOT) and ELISA. No pgp3-specific ASCs were detected in healthy controls, but predominantly IgA ASCs were detected in UK adults with uncomplicated cervicitis or urethritis (P = 0.03, 0.019). In patients with extragenital complications or pelvic inflammatory disease a mixed response with more IgG and IgM ASCs was evident, suggesting a breach of mucosal immune compartmentalization with more extensive infection. In women with chlamydial cervicitis, ASCs secreting predominantly IgA, but also IgG, to pgp3 were present in cervix at presentation, with a frequency 30-50 times higher than blood. Cervical ASC numbers, especially IgG, fell markedly six weeks after antibiotic treatment. We detected principally IgA pgp3-specific antibody secreting cells (ASCs) in children resident in a Gambian endemic area, with a trend towards suppression of IgA responses during intense trachomatous inflammation (P = 0.06), as previously reported for other chlamydial antigens, and in keeping with the findings in genital disease. These data provide a rationale for further studies of immune responses to pgp3 in humans and animal models of chlamydia-induced disease, and its potential use in diagnostic assays and protective immunization strategies.

Adult↗

Validation of a simplified grading of Gram stained vaginal smears for use in genitourinary medicine clinics.

OBJECTIVES: To validate a simplified grading scheme for Gram stained smears of vaginal fluid for the diagnosis of bacterial vaginosis (BV) against the accepted "gold" standard of Amsel's composite criteria. METHODS: Women attending genitourinary medicine (GUM) clinics, as part of a multicentre study, were diagnosed as having BV if three or more of the following criteria were present; homogeneous discharge, elevated vaginal pH, production of amines, and presence of "clue" cells. Women with less than three of the criteria were considered as normal. Simultaneously, smears were made of vaginal fluid and Gram stained and then assessed qualitatively as normal (grade I), intermediate (grade II), or consistent with BV (grade III). Two new grades were used, grade 0, epithelial cells only with no bacteria, and grade IV, Gram positive cocci only. RESULTS: BV was diagnosed in 83/162 patient visits using the composite criteria, the remainder being regarded as normal. The majority of patients with BV had a smear assessed as grade III (80/83, 96%) and the majority of normal women had a smear assessed as grade I (normal, 48/79, 61%), giving a high sensitivity (97.5%), specificity (96%), and predictive value for a positive (94.1%) and negative (96%) test, kappa index = 0.91. Smears assessed as grade II were found predominantly (12/13) among patients diagnosed as normal, with less than three of the composite criteria. Grades 0 and IV were both only found among normal women. CONCLUSION: This simplified assessment of Gram stained smears can be used as an alternative to Amsel's criteria and is more applicable for use in busy GUM clinics.

Body Fluids↗

Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal vaginal microbial flora of pregnant women.

OBJECTIVES: To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora graded as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora. METHODS: A prospective cohort study of pregnant women in an antenatal clinic of a district general hospital. The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora. Two hundred and thirty-seven women were evaluable. Women with abnormal Gram-stained smears (graded as II or III) on clinic recall were randomised to receive treatment (intravaginal clindamycin cream) or placebo and followed to assess outcome of pregnancy, vaginal flora, and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment. RESULTS: Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square (P = 0.2). However, women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic regression analysis model). This may be due to differences in vaginal bacterial species in these grades. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated (revertants) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy. CONCLUSIONS: Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora. Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome, possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen.

Adult↗

A comparison of the use of Papanicolaou-stained cervical cytological smears with Gram-stained vaginal smears for the diagnosis of bacterial vaginosis in early pregnancy.

Our objective is to compare the efficacy of using Papanicolaou (PAP)-stained cervical cytology smears with a standardized method of interpreting Gram-stained vaginal smears for the diagnosis of bacterial vaginosis (BV) in pregnancy. High vaginal smears were Gram-stained and examined by a single observer to characterize 3 grades of vaginal flora and diagnose BV. Cervical smears were PAP-stained and examined for characteristic patterns of vaginal flora including evidence of BV by either a number of cytotechnicians or a single cytopathologist. The results of the 2 methods were compared. Seven hundred and forty-seven women attending an antenatal clinic in a district general hospital who consented to have a smear of vaginal secretions and cervical cytology in early pregnancy. The main outcome measure is the diagnosis of BV by different methods in a pregnant population. Compared with the Gram-stain method for the diagnosis of BV, there was good agreement between PAP-stain interpretation by a single observer but the agreement was not as good with PAP-stain interpretation by multiple cytotechnicians. When the grades were consolidated to normal (grade I) and abnormal flora (grades II and III), compared to Gram-stained smears, PAP cytology undertaken by several cytotechnicians had a sensitivity of 80.7% and a specificity of 90.7%. The sensitivity and specificity increased to 87% and 97%, respectively, when the PAP-stained smears were read by a single cytopathologist. Using kappa scores, only those readings made by a single cytopathologist were reliable. The setting in a cytopathology laboratory comprises multiple cytotechnicians, so that PAP-stain analysis of vaginal smears for the diagnosis of BV is likely to provide results which are less reliable than those obtained by Gram staining. The latter should be the first choice and every effort should be made to set up this service.

Cervix Uteri↗

Recurrent bacterial vaginosis.

Bacterial vaginosis (BV) is a common condition causing an offensive fishy smelling vaginal discharge. Some women have frequent symptomatic recurrences. Our lack of understanding of the trigger factors for the onset and resolution of BV limits our ability to manage these women effectively. Current approaches involve repeated treatment with antibiotics, with or without antifungal agents. Current studies are investigating the value of replacing the vaginal flora with cultured Lactobacillus strains. Control of BV may reduce the incidence of complications including preterm birth and possibly the acquisition of HIV infection.

Anti-Bacterial Agents↗

Characterization of B-cell responses to Chlamydia trachomatis antigens in humans with trachoma.

The circulating B-cell responses to Chlamydia trachomatis of 60 children and 34 adults in The Gambia were characterized in a cross-sectional study of different grades of trachoma, using the enzyme-linked immunospot (ELISPOT) assay. Antibody-secreting cells (ASCs) specific to chlamydial major outer membrane protein (MOMP), heat shock protein 60, and whole elementary bodies were detected in children with no evidence of ocular disease, and the immunoglobulin (IgA) response was significantly increased in those with follicular trachoma. In marked contrast, children with the most intense ocular inflammation paradoxically had an almost completely absent B-cell response of all isotypes and to all chlamydial antigens, but with normal serum IgG and IgA responses, which was even lower than in the group with no ocular inflammation. Adults with or without evidence of trachomatous scarring had equivalent numbers of circulating B cells, principally IgA, to all chlamydial antigens. Plasmablasts secreting antibodies to MOMP were present in the urine of children in the absence of urogenital infection detectable by PCR, and relative numbers were 8 to 25 times higher than in blood, suggesting site-specific homing within a common mucosal immune system. These results suggest that ELISPOT assay of ongoing B-cell responses detects suppression of chlamydia-specific IgA ASCs during the proinflammatory response to ocular chlamydial infection seen in intense trachoma, which may play a role in tissue damage leading to trachomatous scarring.

Adult↗

Sex, thrush and bacterial vaginosis.

Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women of childbearing age. In some women it shows a relapsing and remitting course with apparently spontaneous onset and resolution. There are intermediate patterns of vaginal flora in which lactobacilli and other species co-exist. We asked women with recurrent BV to prepare vaginal smears daily, and to record symptoms, time of menstruation, sexual activity and use of douches or medication. We Gram-stained the smears and assigned a Nugent score for BV, and noted the presence of candida, pus cells, sperm and blood. Eighteen women collected daily vaginal smears for up to 10 months. Forty months of slides were collected in total. Bacterial vaginosis arose spontaneously on 23 occasions. We saw candida arise 11 times. Bacterial vaginosis appeared after candida on 9 of these 11 episodes. We saw BV regress spontaneously 13 times. Nine of these resolutions occurred within 48 h of unprotected sexual intercourse: BV only arose on one occasion within 48 h of unprotected intercourse. The intermediate pattern was seen for up to 10 days, and occurred as BV began or resolved in some women, and sometimes resolved without developing into BV. Bacterial vaginosis arose most often in the first 7 days of a menstrual cycle, and resolved spontaneously most often in mid-cycle. In women with recurrent BV, BV arises most often around the time of menstruation and resolves spontaneously in mid-cycle. Recurrences often follow an episode of candidiasis, and BV often regresses after unprotected sexual intercourse.

Adult↗

Defining bacterial vaginosis: to BV or not to BV, that is the question.

The history of bacterial vaginosis (BV), now extending over more than 40 years, has been remarkable not only in terms of repeatedly changing the name of the bacterium that we now know as Gardnerella vaginalis but also in relation to what is thought to constitute the condition, what it should be called and how the diagnosis can best be made. The composite clinical criteria are often confusing for the nonspecialist, provide room for inter-observer error, and misinterpretation of just one criterion can lead to considerable over or under diagnosis. There is no doubt that diagnosis should be through a Gram-stained vaginal smear, allowing detection not only of 'full blown' BV but also patterns of vaginal flora that while not in this category are nevertheless abnormal. Accurate diagnosis is important in view of the ever-growing list of other important conditions that may occur as a consequence of the abnormal flora. In addition to this, we raise the question of whether the name and abbreviation BV is the best either scientifically or from the point of view of the lay public. While recognizing that it now may be too ingrained for further change, is it possible to have a better term, at least for lay use?

Bacteriological Techniques↗

Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage.

OBJECTIVE: To find out whether women with bacterial vaginosis detected early in pregnancy are at increased risk of preterm delivery. DESIGN: Prospective description cohort study. SETTING: Antenatal clinic in a district general hospital. SUBJECTS: 783 women examined during their first antenatal clinic visit and screened for recognised risk factors for preterm delivery and the presence of bacterial vaginosis or intermediate abnormal flora detected by examination of a vaginal smear stained by Gram's method. MAIN OUTCOME MEASURES: Gestational age at delivery classified as late miscarriage (16-24 weeks' gestation), preterm delivery (24-37 weeks' gestation), term delivery (> or = 37 weeks' gestation). RESULTS: Multiple logistic analysis showed that there was an increased incidence of preterm delivery in women with a previous preterm delivery (9/24; odds ratio 25; 95% confidence interval 9 to 70; P < 0.001) and bacterial vaginosis (9/115; 2.8; 1.1 to 7.4; P = 0.04). A further logistic analysis of data from women recruited before 16 weeks' gestation showed that preterm deliveries or late miscarriages occurred more often in women with bacterial vaginosis (12/77; 5.5; 2.3 to 13.3; P < 0.001). CONCLUSIONS: Late miscarriage and preterm delivery are associated with the presence of bacterial vaginosis in early pregnancy. This is independent of recognised risk factors such as previous preterm delivery.

Abortion, Spontaneous↗

Limited value of two widely used enzyme immunoassays for detection of Chlamydia trachomatis in women.

Enzyme immunoassays (EIAs) are widely used to diagnose chlamydial infections in patients attending genitourinary medicine clinics. They are relatively easy to perform and are suitable for testing large numbers of samples. The objective of this study was to determine what proportion of women with chlamydial infection, defined as the presence of Chlamydia trachomatis in a cervical smear or deposit and/or in the urinary tract, detected by means of a sensitive direct fluorescent antibody test could also be identified by using two commercially available EIAs to test cervical samples. On hundred fifty-one women attending the genitourinary medicine clinic at St. Mary's Hospital, London, were enrolled. The use of the Chlamydiazyme (Abbott Diagnostics, UK) and MicroTrak (Syva, UK) EIAs resulted in the identification of only 56% and 63%, respectively, of women with chlamydial infection detected by direct fluorescent antibody staining. Thus, the EIAs available for detection of chlamydiae in cervical samples are inadequate for identifying all infected women. Improvement might be achieved by testing multiple samples or by resorting to tests of greater sensitivity.

Chlamydia Infections↗

A longitudinal study of bacterial vaginosis during pregnancy.

OBJECTIVE: To determine the longitudinal changes in the incidence of vaginosis in pregnancy. DESIGN: A prospective study of women during pregnancy. SETTING: A District General Hospital in North-West London. SUBJECTS: Seven hundred and eighteen pregnant women attending antenatal clinics. At their first attendance and subsequently, Gram-stained vaginal smears were examined and Mycoplasma hominis and Gardnerella vaginalis were sought by culture. RESULTS: Initially, 87 (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the vaginal smears. Examination of further smears, obtained from 176 women at 36 weeks of gestation, showed that those whose vaginal flora was normal initially, and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis initially, and went to term. In almost 50% (15 of 32) of these a normal lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial vaginal smears graded as intermediate. From this group, six of the 17 (35%) women from whom samples were obtained at 36 weeks gestation still had flora of an intermediate pattern; 10(59%) now had normal flora and only one (6%) had developed bacterial vaginosis. Women with bacterial vaginosis were more likely to be culture-positive for M. hominis than those with normal flora (34/78 versus 10/563, odds ratio 42.73 (18.9 to 102.3) P < 0.001), or to be culture-positive for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio 21.0 (10.75 to 41.2) P < 0.001). CONCLUSION: Pregnant women do not commonly develop bacterial vaginosis after 16 weeks gestation, and if present, it remits spontaneously in approximately half of those who reach term. As bacterial vaginosis is associated with increased rates of second trimester miscarriage and preterm delivery, any treatment aimed at its eradication in pregnancy should be given no later than the beginning of the second trimester of pregnancy.

Adult↗